The present invention relates to therapeutic radiology. More particularly, the present invention is directed to radioactive materials contained in polymers for use in therapeutic applications known as brachytherapy, to structures fabricated of those materials, and to methods of manufacture and use of these fabricated structures.
The local treatment of tissue by exposure to radiation-emitting material is now well established. Such treatment targets the tissue adjacent to the source while keeping the radiation effects on neighboring healthy tissue to a minimum. A major advantage of this form of treatment is that it concentrates the emitted radiation at the site where the treatment is needed, e.g. within a tumor, while keeping the amount of radiation transmitted to the healthy tissue far below what it otherwise would be if the radiation were beamed into the body from an external source, using teletherapy.
Radiation therapy implemented by placing a radiation source near or within the tissue to be treated, ie., brachytherapy, is normally practiced in one of three ways: 1) by placing the source(s) within the tissue to be treated, i.e. interstitial therapy, 2) by placing the source(s) inside a body cavity, normally in association with a positioning device called an applicator, to irradiate tissue surrounding the cavity, i.e., intracavitary therapy, or 3) by placing the source(s) within a vessel or duct, normally in association with a catheter, to treat tissue surrounding the vessel or duct, i.e. intralumenal therapy.
A short segment of gold wire, generally called a xe2x80x9cgold grain,xe2x80x9d containing radiation-emitting gold isotopes such as gold-198, has been found to be a suitable implantable radioactive material. The advantage of using gold grains for interstitial implantation is that gold is compatible with the body. That is, gold neither degrades, dissolves, nor causes any toxic reaction within the body. Radon-222 encapsulated in platinum or other biocompatible metals has also been used in an implantable therapeutic device.
However, materials such as gold-198 and radon-222 have significant counter-indicating characteristics for interstitial tumor treatment in that they emit relatively penetrating radiation, such as high energy gamma radiation. Such high energy radiation not only subjects the patient""s healthy tissue to more radiation than is desired, but in addition exposes medical personnel as well as other persons coming into contact with the patient, to significant doses of potentially harmful radiation. Therefore, it is often preferred to use radiation sources which emit lower energy radiation, such as those that emit low energy X-rays, or beta particles.
The use of capsules enclosing the radioactive material is necessary to contain the radioactive material, preventing it from becoming systemically distributed within the patient or escaping into the environment where it could contaminate medical personnel, medical facilities or the general environment. With the exception of gold grains cited above, such encapsulated radioactive material is referred to as xe2x80x9csourcesxe2x80x9d or xe2x80x9cseeds.xe2x80x9d
The construction of the capsule should preferably allow the rapid and facile insertion of the seed into the organ or body part being treated, with minimal trauma to the surrounding tissue. Due to the small size of the capsules, which frequently have outer diameters of the order of 0.5 mm to 0.8 mm, and lengths of the order of 5 mm, a popular technique for implanting the seeds is to insert them into the body percutaneously using a hollow needle which is preloaded with the desired number of seeds and when the needle is in the desired location in the tissue, a stylet is used to hold the seeds in place while the needle is withdrawn from around them, leaving the seeds in the desired location. The use of such small radiation sources is a common way of practicing interstitial brachytherapy.
U.S. Pat. No. 3,351,049 describes seeds with an encapsulating outer shell containing the radiation-emitting isotope, iodine-125. Iodine-125 has a radiation spectrum that is favorable for interstitial use. The encapsulating shell localizes the radioactive iodine to the tumor treatment site by physically preventing the iodine-125 from migrating to other parts of the body. In particular, this technique protects the thyroid, a site of specific iodine uptake. Therefore, encapsulating an isotope permits the use of isotopes that would otherwise dissolve in the body and/or present potential toxic consequences to the patient. Physicians have employed capsules containing radiation-emitting iodine-125 as part of the treatment of patients with tumors.
U.S. Pat. Nos. 4,702,228 and 5,405,309 describe encapsulated seeds containing palladium-103 as the radioactive isotope. Palladium-103 is a radiation source possessing both a preferred radiation spectrum for therapeutic use and a preferred half-life. Palladium metal is insoluble in body fluids and has been injected as a powder directly into living tissue with no reported deleterious effects. Physicians also have used capsules containing palladium-103 for treating patients with tumors. The entire disclosure of each reference cited hereinabove and below is incorporated by reference.
Brachytherapy has met with increasing success over the past decade, in part due to the availability of more appropriate isotopes such as iodine-125 and palladium-103, and in part due to the recognition of the importance of placement of the seeds within the treatment volume and maintenance of that positioning throughout the therapeutic life of the seeds. The importance of positioning has led to such techniques as computer aided treatment planning routines based on ultrasound or computed tomographic images (Feygelman, V. et al, xe2x80x9cA Spreadsheet Technique for Dosimetry of Transperineal Prostate Implantsxe2x80x9d, Medical Physics, 22, 97-100, 1995), ultrasound guided transperineal implantation for prostate cancer (Brosman, S. A. and Tokita, K., xe2x80x9cTransrectal Ultrasound-Guided Interstitial Radiation Therapy for Localized Prostate Cancerxe2x80x9d, Urology, 38, 372-376, 1991) and conformal brachytherapy for carcinoma of the prostate (Osian, A. D. and Nori, D., xe2x80x9cConformal Brachytherapy for Carcinoma of the Prostatexe2x80x9d, Endocurietherapy/Hyperthermia Oncology, 10, 15-24, 1994).
Imaging technology is available which is capable of accurately locating the desired position for a seed, but holding the seed in the desired position has proven more difficult. U.S. Pat. Nos. 5,342,283, 5,030,195, 4,815,449, 4,754,745 and 4,697,575 all disclose devices intended to assist in initial placement and/or in maintaining placement of the seeds. The objective of all of the disclosed inventions is to provide a means to position discrete encapsulated sources. Positioning is of sufficient significance that a product based on U.S. Pat. No. 4,815,449 is commercially available. The expansion of brachytherapy to the treatment of additional disease types will be facilitated by, and in some cases will depend on, further improving positioning techniques.
The most common brachytherapy sources used for permanent interstitial implantation are small capsules, containing either iodine- 125 or palladium-103, which are approximately 4.5 mm long and 0.8 mm in diameter. In some applications, such as prostate cancer therapy, the availability of a longer seed would be of value in maintaining positioning. However, due to the motion of the soft tissue surrounding the seed, vis-à-vis the rigid capsule of the seed, to use a longer seed would pose too great a likelihood of puncturing a surrounding organ or vessel.
A technique that improves the dose distribution without requiring a longer linear seed is the rigid seed string which is based on U.S. Pat. No. 4,815,449. This device consists of a linear array of iodine-125 seeds spaced at 1 cm center to center inside an absorbable suture material which has been stiffened by a proprietary process. One major drawback to using this device is that it has a tendency to become lodged in the implanting needle due to the effects of moisture on the suture material. Furthermore, this device does not include the ideal source, i.e., a continuous linear source, but rather relies on a series of separated, discrete sources in a line.
Clinical studies indicate brachytherapy sources could provide beneficial therapy in some tumor types where implantation of the seeds directly into the tissue is not possible, for example in the treatment of lung cancer (Nouri, D., xe2x80x9cIntraoperative Brachytherapy in Non-Small Cell Lung Cancerxe2x80x9d, Seminars in Surgical Oncology, 9, 99-107, 1993) In such cases it is useful to insert a series of seeds inside suture material so that they can be sewn into or over the diseased tissue. A commercial product is available from Amersham Healthcare, Model 6720 I-125 Seeds in Carrier, consisting of iodine-125 seeds, spaced at 1 cm center to center, inside suture material. While this product offers a means of attachment, it suffers from representing a series of separated discrete sources rather than a more desirable continuous line source.
Furthermore, a major drawback for metal-encapsulated seeds is that the encapsulating metal absorbs a significant fraction of the radiation emitted by the contained radioisotope, for example about 14% of the iodine-125 X-rays and 40% of the palladium-103 X-rays are absorbed in the encapsulating metal in the current commercial seeds. As a consequence, to obtain the desired radiation dose rate on the exterior of the seed, additional expensive isotope activity must be added to overcome the losses in the encapsulating metal. Also because it is necessary to seal the ends of the capsules, the effective thickness of the metal is not the same in all directions resulting in a radiation field around the seed which is not uniform, a fact that complicates treatment planning and raises the possibility of the existence of areas within the treatment volume in which the radiation dose is below that required to kill all tumor cells present.
Thus the current practice of brachytherapy based on the use of discrete encapsulated sources is limited by: 1) the need to associate groups of discrete seeds together by some means so that they can be placed into tissue in a predetermined array and held in that array throughout the therapeutic life of the sources, 2) the need for complex treatment planning that takes into account the discrete nature of the seeds and the shape of the radiation field around each seed with the assumption the field shape around each seed is the same, 3) the need to add excess expensive isotope to compensate for the radiation absorption in the encapsulating metal, and 4) the creation of a nonuniform radiation field around the source because the effective thickness of the encapsulating metal is not the same in all directions. The present invention as disclosed herein, significantly reduces each of these limitations and furthermore allows a more complete realization of the potential benefits of brachytherapy.
The description of the present invention is facilitated by the use of the following terms which are used in this patent specification and the claims as defined herein:
The term xe2x80x9cpolymericxe2x80x9d means composed of organic polymers, including silicones, whether naturally occurring or synthetic, and whether homopolymers or copolymers.
A xe2x80x9cradioactive compositexe2x80x9d is a substance that consists essentially of a radioactive powder and a polymeric matrix. In accordance with the present invention, the particles of radioactive powder are dispersed within the polymeric matrix essentially randomly throughout a particular volume thereof.
xe2x80x9cTherapeutic sourcesxe2x80x9d that can be fabricated from the radioactive composite include a structure that is solid in cross section, e.g. a right circular cylindrical rod; a structure that is hollow in cross section, e.g. a right circular cylindrical hollow tube; a suture (such as a monofilament or a multifilament thread, cord or string); a mesh; a film; a sheet; and microscopic, essentially monodisperse spheroidal sources.
An xe2x80x9capplicatorxe2x80x9d is a device used to conform a therapeutic source to the shape of a body cavity so as to hold it in place during the period of treatment. Examples of applicators include the Fletcher-Suit and Manchester applicators.
The xe2x80x9caverage dimensionxe2x80x9d of one of the very fine radioactive particles of the radioactive powder is the average of the maximum and the minimum dimensions of the generally irregularly shaped particles.
The present invention provides a novel means for using a therapeutic source without requiring a metallic capsule, thereby producing a radiation field that is substantially uniform in all directions. This novel means is provided by a novel substance, defined as a xe2x80x9cradioactive composite,xe2x80x9d that comprises very fine particles of radioactive material and a polymer. The therapeutic source is assembled from this radioactive composite so as to emit the desired amount of therapeutic radiation when it is used in a patient. In the context of this disclosure, the term xe2x80x9cpatientxe2x80x9d includes any living organism requiring treatment, whether or not human.
The present invention provides a radioactive composite made by mixing very fine radioactive particles, i.e, a radioactive powder, with a polymer, at the time of manufacture, wherein the radioactive material is randomly and essentially uniformly distributed within at least a defined portion of the polymer. This uniformity is a consequence of the large number of particles per unit volume of the polymer and the small size of these particles.
Radioisotopes applicable for use in the present invention include but are not limited to palladium-103, yttrium-90, gold-198 and phosphorus-32.
In preferred embodiments of the present invention, the polymeric matrix is a biocompatible polymeric matrix. Suitable biocompatible materials used for making the biocompatible polymeric matrix include the materials listed in Table 1 and Table 2.
Heretofore, brachytherapy sources intended for permanent interstitial implantation have included a metallic capsule to contain the radioactive material. A significant drawback of these metallic capsules is their non-uniform absorption of the emitted radiation, which causes a reduced radiation dose in certain directions. By eliminating the need for metallic capsules, the present invention overcomes the limitations inherent in their use, thereby allowing the full benefits of therapeutic irradiation from an implanted brachytherapy source.
Brachytherapy devices intended for temporary implantation using iridium-192 also have been designed to work in the absence of a metallic capsule. However, these unencapsulated iridium-192 sources are hazardous to the patient as well as the medical personnel involved, due to the high energy of the radioactive emissions. In addition, these implanted radioactive sources can only be left in place temporarily, causing the patient to undergo both an implantation and a removal procedure, resulting in medical personnel being exposed twice to the radiation hazard.
Conventionally, interstitial implantation of therapeutic radioactive sources is accomplished by placing discrete radioactive sources in a regular three dimensional array in the living body. To a first approximation each radioactive source may be thought of as a separate point source. One drawback of this conventional configuration is that the three dimensional radiation field generated is non-uniformly distributed in all directions and therefore requires considerable effort to be expended by way of imaging, special placement tools and internal spacers in order to assure that the discrete sources are precisely spaced. In contrast, the present invention substitutes a line source for this linear array of discrete radioactive sources, which results in a radiation field which is uniform along its length, and thereby generates a therapeutic array in which any non-uniformity is confined to two dimensions, because the third dimension is forced to be uniform. Thus the substitution of a radioactive line source for a series of discrete radioactive sources in a regular three-dimensional array, simplifies treatment planning, and source placement, and thereby reduces the potential for an area within the treatment volume from receiving a radiation dose that is inadequate to achieve the desired therapeutic effect.
The present invention includes radioactive composites, methods of making radioactive composites, methods of using radioactive composites, materials that are part of radioactive composites, as well as therapeutic sources that are made of or contain radioactive composites.
The therapeutic sources of the present invention can be designed and used as a temporary implant such as one intended to be physically removed after a defined time period or one intended to disintegrate (e.g. to be degraded and/or absorbed by the living body) over a defined time period. Alternatively therapeutic sources of the present invention can be designed to be a permanent implant, i.e., intended to remain for the patient""s lifetime.
The very fine radioactive particles of the present invention are microscopic and are generally irregularly shaped. The xe2x80x9caverage dimensionxe2x80x9d (defined as the average of the maximum and the minimum dimensions) for a suitable radioactive particle can be from 0.002 microns to 20 microns. In preferred embodiments the range is from 0.005 microns to 10 microns. In the most preferred embodiments of the present invention, the range of dimensions is from 0.1 micron to 2 microns. These sizes are in direct contrast to conventional brachytherapy seeds, which are macroscopic in size, e.g. a conventional iodine-125 seed and palladium-103 seed is 4.5 mm long by 0.8 mm in diameter.
The very fine radioactive particles are different from conventional radioactive seeds in important properties other than size. For example, the preparation of the radioactive particles differ from the manufacture of conventional seeds in that the seeds are assembled individually from various components via an expensive manufacturing process, whereas a radioactive powder used in the composite of the present invention can be prepared inexpensively in bulk via a chemical reaction, for example, reduction of metal salts in microemulsion systems. As a result of this difference, production of the radioactive composite of the present invention can be far less costly and far less time consuming than the fabrication of conventional seeds.
In addition, the present invention provides a unique manner for incorporating radioactive material into a therapeutic source. For example, U.S. Pat. No. 5,030,195 teaches that first a mesh or film of polymeric material is formed, and then afterwards radioactive seeds are placed onto it, one at a time. In contrast, the desired film of the present invention may simply be formed in a single step, such as by extrusion or molding from the radioactive composite containing the radioactive particles, and likewise a mesh may be woven or otherwise formed directly from a suture of the present invention.
The present invention provides for varying the amount of radioactivity used for any particular therapeutic purpose. In some embodiments the amount of radioactive particles dispersed in polymer may be chosen from within an acceptable range when the radioactive composite is fabricated. In other embodiments, the amount of radioactivity per particle is selectable at the time of fabrication by either adjusting the amount of the radioisotope added per unit mass of the material making up the remainder of the radioactive particle""s mass, by varying the size of the radioactive particles or both. In a third type of embodiment, the dose is adjusted by varying both the radioactivity per particle and the number of particles dispersed in the polymer as described above.
Still other embodiments allow the therapeutic dose to be varied on the basis of the length of time the therapeutic device is in contact with the tumorous tissue. An embodiment of this type is fabricated to provide the desired dose of therapeutic radiation during a brief period, such as from a few minutes to a day. The therapeutic source of this embodiment serves as a brachytherapy source while it is temporarily associated with the patient, during the prescribed time period. In a preferred embodiment the therapeutic source is temporarily inserted into the patient by means of a catheter.
In one aspect of this invention, the therapeutic source is used to treat a specific localized area in the body of the patient. The therapeutic source is fabricated so that it retains the radioactive particles for at least a defined period of time. In one embodiment of this aspect of the invention the therapeutic source is constructed such that the polymer retains the radioactive particles permanently, preventing any contact between the radioactive material and the patient""s body fluids and tissues. In such embodiments, the polymer is permanent and not adapted to be degraded and/or absorbed by the body.
In another embodiment of this aspect of the invention, the polymer material is adapted to be degraded and/or absorbed by the body. In preferred embodiments thereof, the polymer is selected to disintegrate in the body at a predetermined rate, the rate chosen depending upon the half-life of the radioisotope used in the therapeutic source.
In one use of such an embodiment, the polymer in the therapeutic source is eliminated by the body over time, leaving behind only a small amount of residue from the radioactive particles. In a preferred use, the dissolution time is chosen to be sufficiently greater than the radioactive half-life of the radioactive material, insuring that the remaining radioactivity due to the residue no longer poses a hazard as it migrates from the treatment volume. In a more preferred use of this embodiment, the dissolution time is chosen to be between 10 and 15 times the half-life of the contained radioisotope so that the amount of radioactivity remaining in the residue is between 0.1% and 0.003% of the initial activity.
In a preferred use of such an embodiment, the radioactive particles are comprised of a material which is biocompatible, i.e., chemically inert in bodily fluids and evokes no toxic response when released into the body, so long as the amount of radioactivity remaining in the residue is no more than 0.1% of that originally present. Suitable biocompatible radioactive materials include pure metals, such as palladium particles or gold particles, or coated metals such as palladium particles coated with a layer of a biocompatible material such as titanium, platinum, gold, or a graphite deposit, and insoluble oxides of metals such as yttrium oxide ceramic particles.
Alternative biocompatible radioactive particles include those comprising radioactive materials which are not themselves biocompatible but become so when they are part of an alloy. These alternative embodiments also may be used to provide a powder which can be incorporated into the radioactive composite.
In one aspect of the invention the therapeutic source is used in the treatment of diseased tissue according to the normal practice of brachytherapy in which brachytherapy sources are implanted. A type of diseased tissue which may desirably be treated by this invention is neoplastic tissue. Examples of diseases involving neoplastic tissue include prostate cancer, lung cancer, cancer of the pancreas, breast cancer, head and neck tumors, melanomas or generally solid tumors in soft tissue.
Forms of the therapeutic source comprising the radioactive composite include a structure that is solid in cross section, e.g. a right circular cylindrical rod; a structure that is hollow in cross section, e.g. a right circular cylindrical hollow tube; a suture (such as a monofilament or a multifilament thread, cord or string); a mesh; a film; a sheet and microscopic, essentially monodisperse spheroidal sources.
In one preferred embodiment the therapeutic source is a cylindrical rod, solid in cross section, manufactured to have a preselected degree of flexibility. In a second preferred embodiment the therapeutic source is a cylindrical rod, hollow in cross section. The cross section may be circular, or it may be elliptical or another shape as appropriate. The ends of such rods may be cut at right angles to the axis of the cylinder, or they may be oblique or specially shaped.
A desired degree of flexibility is achieved by choosing the appropriate polymer grade from the commercial supplier of the polymer to comprise the radioactive composite. For suture material, a greater degree of flexibility is desired,
In yet another embodiment, microscopic, essentially monodisperse spheroidal sources can be fabricated from the radioactive composite. Such microscopic, essentially monodisperse spheroidal sources can then be used, for example, in the treatment of primary or metastatic cancer in the liver by infusing the microscopic, essentially monodisperse spheroidal sources into the hepatic artery, the blood flow therein carrying the microscopic, essentially monodisperse spheroidal sources into the capillary network of the liver where they are trapped and deliver their therapeutic dose of radiation. Such spheroidal sources may desirably have any particular diameter from 10 microns to 100 microns, and preferably about 20 microns. To disperse within the small size of the spheroidal sources, the radioactive powder used in this embodiment desirably has an average dimension of 0.002 micron to 0.1 micron.
In certain embodiments of the invention, the therapeutic source is placed in a delivery system and used to irradiate arterial walls and surrounding tissue to prevent restenosis, following procedures to improve blood flow through the artery. In a preferred embodiment the delivery system is a catheter and the therapeutic source is placed at the tip of the catheter. These embodiments can be used with any form of the therapeutic source that can be effectively delivered by these methods. In a preferred embodiment the therapeutic source is a monofilament attached to the distal end of the catheter. In another preferred embodiment the therapeutic source is a hollow tube slid over the tip of the catheter guidewire.
In other embodiments of this aspect of the invention, the therapeutic source is sewn into a diseased tissue in such a way as to deliver a palliative and/or a curative radiation dose to the diseased tissue. In a preferred embodiment the therapeutic source is in the form of a suture, which may be a monofilament or a multifilament thread, cord or string. Examples of applications for this embodiment include intraoperative brachytherapy in non-small-cell lung cancer and control of scar tissue in surgical closure lines.
In still another embodiment, the therapeutic source is a mesh woven or formed by bonding from a continuous suture fabricated from the radioactive composite, and the mesh is positioned in the cavity remaining after the surgical removal of the diseased tissue in such a way as to irradiate and subsequently kill any abnormal tissue remaining in or adjacent to the surgical margins. In a preferred embodiment the mesh can be woven at the time of surgery from radioactive suture, thereby allowing the health care provider to respond in the most appropriate way to the state of the disease as revealed during the surgical procedure.
In another embodiment, a therapeutic source in the form of a mesh, sheet or film is placed inside a cavity of the body to treat diseased tissue surrounding the cavity. The mesh, sheet or film may be used in association with an applicator, as for example an ophthalmic plaque to treat intraocular malignant melanoma.
One aspect of the present invention includes the various means that the radioactive composite can be xe2x80x9cpackaged.xe2x80x9d In some embodiments the radioactive composite is used alone. In other embodiments, the radioactive composite is contained within a second layer of polymeric material. In preferred embodiments of this type, the second layer of polymeric material is not radioactive. In yet other embodiments, the radioactive composite is encapsulated within a conventional metal seed. In still other embodiments the radioactive composite is wrapped around a non-radioactive polymeric core. In yet another form of this aspect of the invention, the radioactive composite is shaped in such a manner so that it encircles a hollow core. In the most preferred embodiments of this aspect of the invention, the radioactive composite contains a radiographically detectable element, e.g. a wire that is radiopaque to X-rays. It is emphasized that all of the embodiments of this aspect of the invention can be applied to all of the forms and shapes of the radioactive composite described herein.
Methods for fabricating therapeutic sources include extrusion, molding, and weaving.
In one aspect of the invention the therapeutic source is a rod that is made of a polymeric matrix manufactured to have a preselected degree of flexibility. The rod is adapted to be inserted into a tissue or an organ to provide a defined radiation field. In this aspect of the invention, the diameter of the rod can be 0.1 mm to 2 mm, with the preferred diameter being 0.2 to 1 mm, and the most preferred diameter being 0.4 to 0.8 mm. The rod can then be cut into any length, with the preferred length depending on the application and the individual circumstances. In preferred embodiments, the therapeutic source is adapted to be cut into short lengths for implantation as a conventional seed, with these lengths being any convenient length, for example from 4.5 mm to 6.0 cm.
In an application of this aspect of the invention involving prostate cancer, the 1-125 and Pd-103 sources have a length of 4.5 mm and are generally spaced 1 cm apart, center to center, when implanted. For prostate cancer, the preferred length ranges from 4.5 mm to 6 cm, a length allowing an entire linear array of discrete seeds to be replaced by a single length of this therapeutic source. Another preferred embodiment has a diameter of 0.8 mm, and is cut into lengths of 4.5 mm.
In another aspect of the invention, a therapeutic source in the form of a rod having preselected flexibility is made by applying a thin coating of a non-radioactive polymer over the radioactive composite. Biocompatible polymers, including those listed in Table 1 and Table 2, can be used as suitable materials to serve as this thin coating.
In another embodiment, a radiographically detectable, e.g. X-ray-opaque, marker wire is included in the rod along or near the long axis of the rod. Following implantation of this particular embodiment, the X-ray-opaque marker can be used to locate implants made from the radioactive composite, by external X-ray imaging. Alternative uses for embodiments containing an X-ray-opaque wire marker include but are not limited to visualization of the therapeutic source on a CT scan and the use of the wire to attach the source to a catheter. Materials that the radiographically detectable element can be made from include, but are not limited to, gold wire, platinum wire, and polymeric material containing a sufficient amount of radiopaque material, e.g. barium sulfate, so as to allow location of the therapeutic source and detection of its orientation by conventional X-ray imaging.
When the radioactive composite is formed in a continuous suture, either monofilament or multifilament, a preferred diameter is between 0.1 and 2.0 mm. This size range closely spans that of suture materials currently available in the medical market. One method for selecting the appropriate length of the radioactive suture to use, is to first determine the desired therapeutic radiation dose that is to be delivered by the suture when it is sewn into the diseased tissue, and then to choose the suture length necessary to deliver this dose on the basis of the radioactivity per unit length of the suture. In a preferred method, both the radioactivity per length of the suture, and the length of the suture are taken into account and jointly adjusted, in order to optimize the delivery of the desired therapeutic radiation dose.
One problem of the conventional brachytherapy sources currently in use is that they produce a reduced radiation dose in certain directions, and thereby create a non-uniform radiation field. Non-uniformity can create regions within the treated tissue where the radiation dose is insufficient to kill all of the diseased cells in that region. The present invention significantly reduces this problem by including embodiments for the therapeutic source, such as a right circular cylinder, manufactured to have a preselected degree of flexibility, that produces a radiation field which is more uniform. For example, the radiation field may be essentially cylindrical along isodose lines in close proximity to the source, having greater symmetry than that of any seed currently available.
In the application of brachytherapy to solid tumors, such as those found in certain diseased prostate glands, radiation therapists have recognized the value of maintaining the individual seeds in a predetermined array. The maintenance of the predetermined array is accomplished in the prior art by taking individual seeds and placing them into an absorbable suture material. The absorbable suture material is then stiffened to provide a group of seeds that are held in a linear pattern at a fixed separation distance. A number of these linear groupings of seeds are then inserted at predetermined spacings and angles into the prostate gland using hollow needles, thereby forming the desired three dimensional array of radiation source within the prostate gland.
By constructing the therapeutic source of the present invention in the shape of a right circular cylindrical rod embodiment, manufactured to have a preselected degree of flexibility, a treating physician is enabled to simply cut sections of the rod to the lengths desired for each of the linear groupings described above and then simply insert these pieces of rod into the diseased tissue. This procedure simply and inexpensively, allows the physician to fabricate any desired three dimensional array of the therapeutic source. Furthermore, the radiation field within the tissue of the present invention will be substantially more uniform because it is created by a series of continuous and uniform line sources.
When neoplastic tissue, such as a breast carcinoma, is removed surgically, the most likely site of recurrence is known to be in the region immediately surrounding the excised tumor. For this reason the surgical removal of such tumors is usually followed by extensive radiation therapy in this region. By constructing the radioactive composite of the present invention into forms such as radioactive sutures or a woven radioactive mesh, a simpler and safer method for irradiating such surgical margins with sterilizing doses of radiation can be accomplished; while still avoiding the damage that otherwise occurs to the surrounding tissue.
Restenosis is the process whereby an artery which has been opened by a technique such as balloon angioplasty, experiences a subsequent reduction in its open cross section, due to cell proliferation or plaque formation. Benign and relatively inexpensive techniques, such as balloon angioplasty, fail in approximately 40% of cases due to restenosis, thereby forcing physicians to perform more expensive, and more dangerous, procedures such as coronary artery heart bypass surgery. The present invention provides a radiation source capable of delivering a dose of radiation to an arterial wall which is intended to reduce the likelihood of restenosis, thereby reducing the number of patients who will ultimately require the more expensive and more dangerous procedures. The therapeutic source for this application is preferably a solid rod, manufactured to have a preselected degree of flexibility, or a hollow tube. Such a source must be flexible enough when associated with a catheter to be maneuverable into the treatment site.
The detailed description of the invention, provided below, will aid in the overall understanding of the invention. However, one skilled in the art will immediately realize that the methods, results and examples presented only help illustrate how the invention works and are not meant to limit the scope of the invention as defined by the appended claims.